In
the basement of the Vaccine Research Center (VRC)
at Yerkes Main Station at the end of Gatewood Road live
thousands of rats, mice, and voles. Their tiny claws scrape
the bottoms of stacked, ventilated cages, through which one
can glimpse the rodents translucent ears, hairless tails,
and twitching noses.

While
it might seem like a storeroom for the NBC
challenge series Fear Factor, which calls on contestants
to face their phobias, this sterile environment of glass and
steel is actually the place at Emory where most clinical vaccine
trials begin: the vivarium.

Not
that the vivarium doesnt have its own dangers. Its sophisticated
ventilation and decontamination systems are necessary to comply
with Biosafety Level 3 standards for researchers who study infectious
agents like HIV and malaria.

While
primates have received much of the publicity, especially at
Yerkes, rodents are still the most common animals used in biomedical
research, due to their rapid maturation and high breeding capacity.
Federal law mandates that the safety and efficacy of experimental
drugs and vaccines be tested in animals prior to undertaking
human trials.

The
order is generally mice to monkeys to humans, says Rafi
Ahmed, professor of microbiology and immunology and director
of the VRC.

Since
its inception in 1995, the Vaccine Research Center, with twenty-three
state-of-the-art laboratories and a cadre of internationally
known researchers, was conceived as a one-stop shop,
where experimental vaccines developed on-site could also be
tested. Last year, with the opening of the VRCs
Hope Clinic on Church Street in downtown Decatur, this vision
was realized. The Hope Clinic is the first facility in the country
dedicated solely to testing vaccines in clinical human trials.

The
first Hope vaccine trial began in Februaryfourteen volunteers
were given a new HIV vaccine developed
by Merck, one of the largest pharmaceutical vaccine manufacturers
in the world.

Atlanta
seems to be a receptive place to do HIV
vaccine trials. The community here really wants to make a difference,
says Mark Feinberg, director of the clinic.

Merck
chose Emory as one of eight test sites in the country for phase
one trials of its experimental AIDS vaccine,
which was developed from selected proteins of HIV
rather than the whole virus and is designed to elicit a targeted
immune response. One of a new breed of DNA-based
vaccines, it does not prevent infection but reduces or eliminates
viral particles in the body. DNA vaccines
can be manufactured inexpensively in a shorter period of time
than conventional vaccines and are less fragile.

Developing
a safe, effective, and affordable vaccine to prevent HIV
infection is the Vaccine Research Centers primary goal,
Ahmed says. AIDS vaccines have been especially
hard to develop because of the nature of the virus, which destroys
the very immune cells a vaccine enlists.

HIV
is constantly changing and mutating, so it presents a moving
target, essentially, Ahmed says. You have to understand
both the virus and the immune system to develop an effective
vaccine.

Another
promising DNA-based AIDS
vaccine, developed at Emory by Harriet Robinson and colleagues
Rama Rao Amara and James Smith, will be moving into human trials
this year, after showing success in primate trials. The multiprotein
vaccine requires three shotstwo DNA-based
inoculations to prime the immune system, followed by a booster.

Many
other experimental vaccines are being developed at Emorys
VRC as well, to combat diseases including
malaria, measles, herpes, and influenza.

Robinson,
Ted Ross, and researcher Yan Xu have successfully engineered
and tested a single-dose, DNA-based influenza
vaccine in mice, which could serve as a model for more effective
vaccines against a variety of viruses, including HIV.
Since new strains of the influenza virus are constantly emerging,
guarding against a flu epidemic with conventional vaccines involves
anticipating the next strain. But DNA
vaccines could be made quickly enough to be distributed after
the specific influenza strain is identified.

The
Bill and Melinda Gates Foundation has awarded a three-year,
$885,000 grant to Robinsons lab to support her ongoing
research to develop a DNA-based vaccine
for measles. Robinson is collaborating with Diane Griffin of
Johns Hopkins University and Paul Rota of the Centers for Disease
Control and Prevention (CDC).

Measles
kill about 900,000 people a year and remains endemic in many
developing countries because children either do not receive
the vaccine or they receive it too early. If a child is younger
than fifteen months, maternal antibodies are so plentiful in
his or her blood that the measles vaccine antibodies fail to
develop. Robinson and her team are working with rhesus monkeys
to develop DNA measles vaccines that are
effective in the first year of life.

Another
worldwide killer is malaria, which is carried and spread by
mosquitoes and infects three hundred million to five hundred
million people a year. It is prevalent in tropical regions,
including parts of Africa, Southeast Asia, South America, Central
America, and India. Mary R. Galinski, a VRC
investigator and assistant professor in the infectious disease
division of the School of Medicine, and Yerkes scientist Alberto
Moreno are conducting trials in primates to assess the safety,
dosing, and effectiveness of several malaria vaccines. Galinski
is also studying the genetic and biological make-up of plasmodium,
the organism that causes malaria.

Samuel
H. Speck, director of the Center for Emerging Infectious Diseases,
is investigating herpesviruses and the Epstein-Barr virus. A
major property of herpesviruses is their ability to persist
for life. Speck is trying to determine how these viruses avoid
their victims immune response and how they reactivate
after long periods of latency.

The
VRCs research is funded by an array of private and governmental
grants, including the Georgia Research Alliance (GRA),
the CDC, the National Institutes of Health,
and the Gates Foundation. Funding totalled $18 million last
year and is expected to be even higher this year. The GRA
also provides funds for salariesAhmed is the GRA
Eminent Scholar in Vaccine Research and Speck is the GRA
Eminent Scholar in Emerging Infectious Diseases.

The
VRC has established its own start-up company,
GeoVax, through which it will eventually be able to market its
vaccines. In the near future, Ahmed says, VRC
scientists will be working toward vaccines for hepatitis C and
certain types of cancer.

In
research and academia, he says, we are always looking
to move forward.